The leech has proved to be a particularly favorable preparation for studying a number of general problems concerned with integrative mechanisms, regeneration and the physiology of neuroglial cells. Its nervous system consists of a chain of stereotyped, segmental ganglia, each of which contains relatively few cells. A number of individual neurons have been unambiguously identified, their synaptic connections mapped and their functions established as sensory or motor. One aim of our experiments is to determine how use and disuse affect the transmission of signals in certain well-defined reflex pathways that we have shown to contain both chemical and electrical synapses. Another is to assess the physiological consequences of the extracellular K accumulation that occurs when neurons fire at natural frequencies. The third problem concerns the specificity of regeneration by individual nerve cells, whose connections have been interrupted by a lesion; in a preparation such as this, one can study whether nerve cells reestablish specific connections with the correct target cells, within the central nervous system and in the periphery.